An abnormal thrombin, or dysthrombin, has been purified after fragmentation of Prothrombin Quick, a unique prothrombin variant from a patient with dysprothrombinemia. The goal of the research is to study the enzymology of the dysthrombin, with a primary objective to determine whether the defect is in substrate binding, catalysis, or both. The activities with synthetic substrates suggest a defect in catalysis, while studies with fibrinogen show a defect in both binding and catalysis. Studies are planned to determine which other substrates show a binding defect. Pre-steady state kinetics will be used to measure precisely the relative defects in acylation and deacylation rates. Further studies will use the dysthrombin as a reagent to probe the role of thrombin in platelet and endothelial biology.